Food allergy (FA), defined as an immunoglobulin (Ig) E-mediated hypersensitivity reaction to food, is a growing clinical and public health problem in the U.S. and worldwide. The role of vitamin D deficiency in the development of FA is of great interest, given widespread vitamin D deficiency in the U.S. population, its nearly parallel epidemiological and geographic patterns with the prevalence of allergic diseases, and its recognized role in regulation of immune responses. To date, no study has been conducted to evaluate the effects of vitamin D deficiency on the development of FA, nor gene-vitamin D interactions. The central focus of this proposal is to investigate whether cord blood 25(OH)D concentrations are associated with the development of FA, and whether such associations can be modified by individual genetic variants, using the extensive resources of the Boston Medical Center (BMC) Birth Cohort. This cohort consists of ~9,000 mother-infant pairs enrolled or being enrolled at the BMC. The information collected at the initial recruitment includes comprehensive pre- and peri-natal epidemiological and clinical variables along with maternal and cord blood samples. This cohort has been followed from birth onward to identify incident cases of FA and other allergic diseases. The information collected at postnatal follow-ups includes FA questionnaires;medical records including ICD codes of physician diagnosis;child's venous blood sample;and total and food- and aero- allergen-specific IgE. A nested case-control study will be conducted, including 400 FA incident cases and 800 asymptomatic and non-sensitized controls identified from the BMC Birth Cohort. Two primary aims will be accomplished: (1) To assess the association of cord blood plasma (CBP) 25(OH)D concentration with the development of FA with adjustment for potentially important prenatal and postnatal confounders. (2) To assess the gene-vitamin D interaction effects on the development of FA, with adjustment for important covariates, population admixture, and multiple testing. This study will focus on all potentially functional SNPs in the following genes/regions: (1). To be identified from genome-wide association study (GWAS) of FA (R56 AI080627);(2). To be identified from candidate gene study of FA (R21 AI079872);(3). To be generated by Ingenuity Pathway Analysis given the above identified genes;and (4). Known to be involved in 25(OH)D metabolism and regulatory pathways. This proposal is strengthened by: using a large, existing birth cohort;an innovative approach by integrating individual genetic susceptibility with an objective biomarker for assessing vitamin D status;a large sample size that assures adequate statistical power;and a highly interactive and experienced research team. The findings from this study will not only help establish causal relationship between low vitamin D and development FA in newborns, but will also enhance the ability to identify newborns who are genetically susceptible to the effect of low vitamin D. Ultimately, this can lead to design targeted, cost- effective clinical and public health interventions with the goal of preventing or reducing the incidence of FA. Food allergy (FA) is a major clinical and public health problem in the US and worldwide;and is also the most common cause of emergency room visits for anaphylaxis. Low vitamin D level in early life may be one of the risk factors for the development of FA. The main focus of this proposal is to help us understand if cord blood vitamin D concentrations are associated with FA and if such associations can be modified by individual genetic variants, which has never been investigated before.